Disturbed Development of the Preimplantation Embryo in the Insulin-Dependent Diabetic BB/E Rat

Although improved regulation of maternal IDDM during pregnancy has resulted in a major fall in the stillbirth rate, the rates for other problems, such as spontaneous preterm labor, fetuses small for gestational age, congenital malformation, and the incidence of large placentas, remain raised. This has suggested the possibility that the damaging effect of conventionally treated but poorly regulated IDDM may operate primarily at the earliest stages of gestation, even before the diagnosis of pregnancy has been made. This study shows that spontaneous autoimmune IDDM in the Bio Breeding/Edinburgh (BB/E) rat is associated with severe disturbance in the development of the preimplantation embryo in a majority of pregnancies, as indicated by a fivefold increase in the incidence of degenerate fragmented embryos and a 33% reduction in the number of expanded blastocysts and in those blastocysts that reach the expanded stage a 20% cellular deficit in the inner-cell mass without any change in trophectoderm cell number. In addition, we find that blastocysts removed from diabetic rats and cultured in vitro for 24 h show no sign of “catch-up” growth of the inner-cell mass, although under these conditions, the trophectoderm exhibits a 25% cellular accretion. It is tempting to speculate that these phenomena are a presage of the characteristic combination of fetal growth retardation and large placentas, which are a feature of both BB/E rat and human IDDM pregnancy.